Coating of endoprostheses with a coating consisting of a tight mesh of polymer fibers

ABSTRACT

The present invention relates to grid-like or net-like endoprosthesis having a continuous, respectively ongoing and interstices-spanning coating with a thread-tangle, wherein this continuous, respectively ongoing and interstices-spanning coating covers the struts as well as the interstices between the single endoprosthesis struts.

The present invention relates to endoprostheses coated with a polymericclose-meshed thread-tangle as well as the manufacture and use of the socoated endoprosthesis.

Pathological changes and injuries to the vascular walls in and at allbody passages and body openings may lead to painful inflammations,constrictions, occlusions, sacculations and bleeding of these passageways, so that the correct functioning of the hollow organ is impaired oreven impossible. Degenerative diseases of the vascular walls representwith over 80% of the cases the most common cause for heart infarction orstroke in general. Poor nutrition, the widespread disease diabetesmellitus or also excessive smoking can lead to pathological andarteriosclerotic changes of the vascular passage, which can alsomanifest in the leg arteries and if not treated properly lead tonecrosis and ultimately to amputation of the affected extremities.

Likewise life-threatening is the formation of aneurysms. These aresacculations of the vascular wall that can be traced back to an innateweakness of the connective tissue, arteriosclerosis, inflammations ortraumas, or may be generated as the result of a volume load of thevascular wall. In this context it is mentionable that aneurysma spuriumis also known as false aneurysm. Thereby a rupture goes through theintima and media of the vessel. This can be the result of a blunt orsharp injury, as it occurs after arterial puncture such as afterpuncture of the artery in the groin when conducting a PTCA and/or stentimplantation as well as after heart catheter examinations. The probablereason therefore is assumably an insufficient pressure after removal ofthe catheter, so that the blood vessel is not closed properly leading tobloody oozing into the surrounding tissue.

Another and likewise commonly occurring danger affecting body passagesis the growth of malignant and benign tumors. Rapid and uncontrolledcell division leads to the spreading of the tumor at and in holloworgans and thus to obstructions or occlusions of hollow body passages.Examples are esophageal cancer, cancer of the hypopharynx, nasopharynxand oropharynx, intestinal cancer, lung cancer, kidney cancer,occlusions of the bile duct, the pancreas and the urethra etc. Furthercauses for the impaired functioning of cavities can be cyst and fistulaformation.

Stenosis in general refers to a physical obstruction or an interruptionof the function of vascular cavities. Restenosis is a recurringstenosis, wherein the cause can be the initial treatment of a stenosis.

For treating constricted, blood-carrying body passages and for treatmentof stenosis and restenosis, alongside the percutaneous transluminalangioplasty (PTA) or the percutaneous transluminal coronary angioplasty(PTCA), in the last two decades the stent has proven its worth aspermanently in the body residing endoprosthesis with possibly locallyacting active agent therapy. It is implanted directly with a ballooncatheter and fixated during the PTA or PTCA, meaning during expansion ofthe affected site with a balloon catheter or after removal of theconstriction at the affected site with atherectomy catheters. The stent,in its expanded form, presses the vascular wall outwards in a way thatthe native vessel diameter of the affected vessel is restituted and thevessel are kept open.

However, the foreign material of the endoprosthesis as well as theoperation itself provokes protective reactions of the body. Theendogenous defense system reacts thereupon within a short time throughdifferent paths such as humoral and specific immune reactions,hyperproliferation of cells, thrombus formation etc. that lead to anoperation and therapy induced restenosis, if no further mitigatingmeasures are taken.

Efforts in the continued development of endoprosthesis towards animproved biocompatibility of the used material, an increased flexibilitycombined with a reduced fatigue of material and a reduction of theforeign surface shall continuously minimize the risk of foreignsurface-induced restenosis rate at least in the cardiovascular andperipheral vascular area.

Besides said basic requirements for such endoprosthesis with minimizedforeign surface, the coating of the surface with biocompatible,biodegradable or biostable materials showed to be a promisingadvancement which mostly acts as a matrix for an anti-restenotic actingactive agent. This active agent shall stop the pro-restenotic process bya time- and concentration-adjusted active agent release according to therequirements and ideally promotes the process of healing as good as inthe ideal case of non foreign-influenced healing. Herein therequirements to the endoprosthesis itself, the coating material and theactive agents as well as their interactions are equally high.

The same scaffold is used for relieving, preventing stenoses in all bodypassages, or for impeding the threatening obstruction as long aspossible (such as in the palliative medicine or in the pain medicine),for example in the esophagus, bile duct, intestine, lung, kidney,urethra, pancreas, cerebral vessels, trachea (trachea bronchiale),paranasal sinus and other body cavities.

Hence, the task of the endoprosthesis is to stop the growth ofexcessive, malignant, benign and/or disturbing tissue in general intothe lumen, preventing inflammations or reducing, preventing or remedyingthe risk of sacculation formation of hollow vessels. Alongside vascularrestenosis caused by stents, furthermore, tumor growth, inflammationsand aneurysm such as cyst formation, fistulas, traumas and scarformation shall be named as reasons for use of such endoprosthesis.

In contrast to vascular stents combating atherosclerosis these stentsare hence provided with a preferably polymeric lining covering theentire cylindrical stent body including the interstices between thestruts that should impede or at least delay also as an effectivemechanical barrier the renewed ingrowth of the tumor through theinterstices into the lumen.

It is common to all foreign materials used in body cavities that theyensure the highest possible unlimited flexibility, i.e. thephysiologically necessary undisturbed, native motility of the targetorgan, and at the same time removing or delaying the occurred localdisturbances of the hitherto normal conductivity. This flexibility isdetermined by the material and the design of the hollow body and has ledto a wide-meshed, respectively net-like structure with a comparativelylow vascular wall contact area.

According to symptoms and application site different requirements forthe implant properties have to be taken into account. Thus for anendoprosthesis bound to be implanted into an artery there are differentrequirements than for example for an endoprosthesis destined to beimplanted into the esophagus, bile duct, trachea, cerebral artery,paranasal sinus access, oropharynx, hypopharynx etc.

The vascular coated as well as the uncoated stent for the treatment ofarteriosclerosis or stenoses and the prevention of stent-inducedrestenoses have the least possible foreign surface, as the currentlycommercially available products demonstrate.

There is a plethora of patent applications and patents in this field. Asbeing effective, above all three competing stents are prevailing asmarket leaders. First, this is a polymer-coated stent eluting the activeagent paclitaxel (Taxus stent from Boston Scientific Corp.), on theother hand a polymer-coated stent eluting the active agent rapamycin(Cypher stent from Cordis Corp.) as well as the stent Xience V (AbbottVascular) eluting the sirolimus derivative everolimus.

Though the results and experiences with these and other coronarydrug-eluting stents (DES) are very promising and represent a positivecontribution to restenosis prophylaxis in the cardiovascular field notall problems are solved. For example, there is the phenomenon ofin-stent restenosis such as late stent thrombosis (LST), as well as thefinding of the optimal polymer. Despite good results the search for evenmore optimal active agents is going on in order to further reduce therestenosis rate as well as late complications.

An endoprosthesis used in tumor treatment can only constitute a barrierif it is able to cover the affected area completely, i.e. full-sizecoverage. This is only possible if the interstices of the surfaceminimized endoprosthesis don't remain passable, as only then the barrieris able to impede or retain tumor growth into the lumen.

As the polymer wrapped stent shall fulfill its function adapted to thesite of action in a safe manner and in the ideal case shall ensure or atleast support, but not bias in a negative way or even disturb theunhampered function of the target organ, different concepts have beenelaborated in the past through which a stent shall be provided with apolymeric sleeve.

Thus WO 93/22986 describes a self-expanding esophagus stent which iscovered with a silicone tube on its central section and which compressesthis section in such a way that the stent has a lesser diameter than thetube-free proximal and distal end sections. The proximal and distal endsare not covered for enabling a better fixation of the stent to thecavity walls by means of the free stent struts. But this stent didn'tturn out to be successful because problems are arising by theconstriction of the stent body, for example during vomiting the forcesacting on the stent are so increased that the stent is moved and injuresthe esophageal wall with its free stent ends.

Further the silicone tube can be torn or it can detach under thesecircumstances and mucus or food particles can settle between thevascular wall and the silicone coating so that apart from the threat ofinflammation several scenarios utterly negative for the patient maybecome realistic.

WO 2005/030086 describes a method for full-size coating of a likewiseself-expanding stent body with a polyurethane sleeve in which after afirst spray coating of the stent with a polymer the polymer is imposedto the struts from the inside as a foil by means of a balloon or anothersuitable cavernous template. Herein the coating covering the entirestent occurs from the luminal side so that on the exterior side thestent struts keep on stabilizing the stent in the wall of the cavity.The subsequent heating of the system beyond the softening temperatureshall bind the polyurethane to the stent. Problems arise since thepolymeric sleeve is not quantitatively or completely bound to the coatedstent and therefore does not remain permanently on the stent under thegiven circumstances. Likewise small holes may form through the heatingthat in the case of implantation may possibly enlarge and finally maylead to a detachment of the coating material and even to adelocalization of the entire stent.

Furthermore, the heating beyond the softening temperature of the polymermay lead to a situation wherein on the one hand the coating on theabluminal surface of the stent struts softens and invades theinterstices between the struts and thereby the polymer coat does notonly adhere to the stent, but also to the balloon likewise consisting ofa polymer, so that during dilatation the coating can rupture or thestent does not detach from the balloon. Thus on retracting the balloonthe interior coating has adhesion problems and is detached at leastpartially when the balloon is removed from the stent. As a result, foodor mucus can settle between the detaching coating and the interior wallthat step-by-step severs the coating from the stent but above allhampers the undisturbed passage. The detaching material stands out intothe cavity and leads to additional irritations, nausea or cough whichsupports or rather is the cause for defixation of the entire stent.Currently, a commercially available esophagus stent is the ALIMAXX-ES™,which is a completely encased vascular support with a smooth PU-polymersleeve (as foil).

A further field of application of stent-strut-interstices-overlappingcoated stents is in the field of tracheal stenoses, most commonly causedby bronchial carcinomas, which are currently holding the second place inindustrialized states in the ranking of the incidence rate of malignanttumors. These tumors can hardly be healed by surgery or by means of amultimodal therapy so that ca. 30% of the patients diseased of astenosis of the central airways also die on it.

A special problem in this field arises from the shape of the tracheawhich is not round, in contrast to other hollow passages, so that therisk that a stent detaches itself and likewise that mucosa gathersbetween the coated stent and the tracheal wall is particularly high forthese stents. A similar unfavorable situation results when the coatingdetaches from the stent under the given circumstances and secretion maysettle between stent and coating. The risk of detachment of the coatinghas to be taken into account for all coated vascular supports to thesame degree and in all fields of application, also cardiovascular.

Most commonly, the so-called Dumont stent is still used, a tubularsilicone tube with naps for a better fixation on the abluminal side,specifically developed for the trachea area, since it can be removedmore easily in contrast to most metal stents, because due to commonlyoccurring subsequent complications re-implantation is often necessary.

The different commercially available metal stents (e.g. the nitinolstent, gianturco and wall stent) are nowadays often used in a full-sizecoated form but likewise still don't show the desired success.

Because of the conditions in the trachea the migration of a foreign bodyis still an improvable problem. In addition to the poor fixation comes adisadvantageously high wall thickness, as present e.g. in the Dumontstent, impeding the secretion flow along the interior wall surface, i.e.luminal. This causes an accumulation of secretion by which the airstream is impeded again, which leads to inflammations and favorscolonization by germs.

These “restenoses” are a commonly occurring complication. Thus there isa stent-induced restenosis risk not only with the conventionaldrug-eluting stent (DES) in the coronary field but also for full-sizecoated products, i.e. consistently coated products such as a tube, thissubstantial risk of a new occlusion or constriction of the coated stentwith e.g. bronchial secretion has to be taken into account which in theend can only be removed surgically as a viscous rubber-like mass.

Another common cause for the occlusion or the increased adhesion ofmucosa lies in the desiccation of the luminal stent surface since thebody-regulated moisture of a native interior wall is not given anymorebut is necessary for allowing the bronchial secretion to flow off. Itadheres in this dry area and thus is accumulating ever the more, as thebreathed air alone can't maintain the necessary moisture in this segmentfor ensuring a natural equilibrium, as is warranted by the mucousmembranes. Thus the affected patients depend upon the regular inhalationof liquid nebulizers in order to delay the infallibly occurringobstruction with secretion as long as possible.

Another and for the patients utterly unpleasant social problem is theextremely malodorous breath caused by the in situ colonization ofbacterial germs on the implant surface, since the colonization by germsat these sites can't be averted anymore under the given circumstances.Locally occurring inflammations of the most diverse origin but also as aresult of the stent implantation are likewise causal for a newocclusion.

The AERO® stent from Alveolus tries to contain this problem, but is noyet fully developed. The stent also has a very smooth foil-like coatingmaterial such as the esophagus stent ALIMAXX-ES™ already describedabove.

The same scaffold of a stent coated with some kind of foil can be usedfor treatment of aneurysm. The cause of aneurisms is the pathologicsacculation of the vascular wall in which blood is gathering andcoagulating. Due to the weight load the vascular wall stretches evermore at this site, resulting in further blood flow, stagnation andclotting. Besides the increasing threat of thrombosis this finally leadsto a vascular rupture.

U.S. Pat. No. 5,951,599 envisages to solve this problem by filling thefree interstices of a vascular stent with a small-meshed partiallyapplied polymeric network which is positioned over the sacculation inthe blood vessel and will cover the aneurysm in such a way that theblood flow comes to a standstill in the sacculation. As a consequence astable thrombus is formed therein, thereby stopping the enlargement ofthe aneurysm. Further, the polymeric coverage shall prevent that thethrombus or parts of the clot are spilled into the blood circulation andcan cause an infarction elsewhere. Here the same problems arise, too,because of bad adhesion of the polymeric network which deprives thestent of its function and thus leads to an increased risk for thepatient. Currently, aneurysms are still treated by filling them withmetal wire (“coils”) which shall stop the blood flow inside thesacculation. But also the commonly and necessarily used artificialinlets or artificial outlets to hollow body organs are insufficient,when used for longer time periods of time. Painful inflammations andbacterial infections result in frequent changes of the inlets andthereby to complications and additional intolerable and risky stress forthe patient. Hence, it is important to find a solution that assuressafety of the patient.

It is the objective of the present invention to provide a coatedendoprosthesis and in the case of endoprosthesis with interstices suchas stents to provide interstices-overlapping or interstices-coveringcoated endoprosthesis, which avoid the described disadvantages for allbody passages including the coronary fields of application and whichunder consideration of the conditions existing at the application siteprovide an optimal, uniform production method for such implants.

This task is solved by the technical teaching of the independent claimsof the present invention. Further advantageous embodiments of theinvention result from the dependent claims, the description and theexamples.

It was found that the problems of the state-of-the-art can be solved bymeans of an endoprosthesis the surface of which has a coating of athread-tangle. The coating is preferably a sprayed thread-tangle. Hence,an inventive endoprosthesis has a surface coated at least partially orcompletely with a polymeric close-meshed or tight-meshed thread-tangle.Moreover it is preferred, if the thread-tangle coating, i.e. the coatingof thread tangle, reaches over the ends of the endoprosthesis andthereby covers sharp edges or prevents exposed strut regions.

The thread-tangle coating is flexible, mechanically stable and consistsof a polymeric material consisting of threads, which are orientedstatistically and randomly and are tangled and linked with each otherand have meshes that are formed by the surrounding threads. The singlethreads of the thread-tangle coating consist of the polymeric materialand in particular of the herein mentioned polymers. These polymers havepreferably a high average polymerization grade.

This thread-tangle can be applied as coating to full-size, tubularendoprosthesis such as bladder catheters, bypasses and artificial stomaeoutlets as well as on so called stents. A stent is to be understood as agrid-like or net-like endoprosthesis. A stent does not form a massivetube but a grid-network. A stent for example is cut out of a massivetube e.g. by means of a laser, leaving only single preferably thinstruts connected together. The term “struts” as used herein shall beunderstood as single solid segments (stent struts) of the scaffold ofthe endoprosthesis or stent that are interconnected at nodes and therebyform the expandable and flexible structure of the endoprosthesis.

On cutting a stent segments between the single struts are cut out whichshall be named “interstices” herein. Thus an endoprosthesis has aplurality of solid scaffold components (e.g. struts, in form of rings,spirals, waves and wires) that build the endoprosthesis, as well as aplurality of interstices between the solid components. In commonembodiments of endoprostheses the struts converge in nodes so that theinterstices are defined by the surrounding struts and nodes. There are,however, endoprosthesis embodiments having no or nearly no nodes and thestruts having for example the form of rings or spirals. In suchendoprostheses there is for example partially no plurality ofinterstices anymore but only a few or only one interstice defined forexample by two intertwining spirals. Then such interstices are notcompletely bounded anymore but can have one or two or also more openends or open sides. Anyway, “interstices” refer to the open or boundedarea between the solid endoprosthesis components.

A thread-tangle coating according to the invention is appliedinterstices-overlapping on a stent, i.e. the interstices formed by theinterstices enclosing struts are also coated. Thus, this coating spansthe interstices of the single struts, like a bridge, which is onlytethered at the scaffold, the struts, and the interstices do not rest onsolid ground. A thus generated lining may refer to the entirecylindrical stent body or only as to selected areas thereof. Forexample, optionally either proximal or distal segments, the centralsection, single segments or stents coated half-side in longitudinaldirection and of course also combinations of these areas can be coated,according to the indication. The coating is applied preferably on theouter side, i.e. the side facing away from the lumen (abluminal). Butdepending on the indication the lumen facing side can also be coatedwith a coating of a polymeric close-meshed or tight-meshedthread-tangle. It is also possible to coat both sides.

The term “interstices-overlapping” as used herein refers also tointerstices-spanning or interstices-covering and hence clarifies that incomparison to other coated stents the coating is not only around thestent struts, but is all around the whole stent. This can be seenespecially well in FIG. 3 and FIG. 7C. FIG. 3 shows a thread-tanglecoating around a stent and the luminal metallic surface of the stentstruts can be seen through the torn open parts. Furthermore, it can beseen that the coating of the thread-tangle is not around the singlestent struts but only adjoining at the abluminal surface of the stentstruts wrapped around the whole stent. FIG. 7C shows how the coating ofthread-tangle covers the whole stent like a textile coat and the stentpattern pressing lightly from inside of the thread-tangle coating iswell recognizable.

For the coating are used supports for all body passages or bodycavities, commonly also named “vessels”, such as arteries, veins,esophagus, bile ducts, kidney ducts, hollow passages in the nose andmouth region, trachea, bronchial channels, duodenum segments, colon orother approximately tubular body passages, wherein this preferable groupof endoprosthesis has a grid-like or net-like structure, as for examplea stent. The term “body passages” or “vessels” comprises herein not onlynatural body passages or body channels but also artificial body openingsand body channels as for example bypasses and artificial stomae. Furtherapplications for endoprosthesis coated according to the invention thusare larynx implants, bypasses, catheters or artificial stomae and ingeneral all areas in or at the living organism where the body passagehas to be kept free as well as motile, wherein the vascular walls arenot isolated completely from the lumen side, so that the necessarycontact between the inner vessel wall and the lumen is ensured. By thisway an isolation of the cavity wall from the lumen is preventedconcerning the important substances in the lumen that are necessary forthe preservation of the health of the inner cavity surface. Thepermeable coating allows the exchange, transport and delivery ofsubstances that are important for the preservation of function betweenlumen and cavity surface such as liquids, moisture, nutrients ormolecular substances necessary for preservation of the function. Therebythe impact of the implanted foreign body on the surrounding is reducedto a minimum.

Such a coated endoprosthesis can be adapted for individual applicationsby thread diameter, thread length, mesh number and mesh size, pore sizeand pore formation, degree of cross-linking and inter- and eventuallyintrafilamentary permeability of the tangle according to correspondingneeds in the target vessels.

A thread-tangle as well as a thread-tangle coating consists of looselyand randomly arranged fibers or threads that because of their confuseand random unorganized structure are difficult to be separated intosingle fibers or threads. The consistency of a thread-tangle and of thethread-tangle coating thus depends on the adhesion intrinsic to thefibers and on the confuse, random and unorganized structure. Thethread-tangle can be additionally solidified to which end differentmethods can be used such as temperature, light, moisture and/orpressure. A solidified thread-tangle is preferred as coating in theorganism because detachment of threads that could cause complications isprevented thereby. The mutual adhesion of the threads and thus thesolidification results herein in the ideal case already during thedrying procedure through the evaporation of the solvent. Also after thedrying procedure the thread-tangle coating is tearproof, expandable andcompressible, respectively crimpable (i.e. able to be mounted on acatheter balloon). Sterilization of the endoprosthesis (heatsterilization with hot air and steam, fractionized sterilization orchemical sterilization with ETO, ozone, formaldehyde, hydrogen peroxideor peracetic acid) must also be possible without having any influence onthe structure or permeability of the thread-tangle however the methodmust be adapted to the properties of the used material of theendoprosthesis.

A thread-tangle according to the invention is a textile planar productof single fibers or threads that are not interweaved, knitted or braidedor are otherwise connected or jointed in a specific pattern with eachother. In contrast, tissues, knitted and weaved fabrics, are produced ofyarns and membranes of foils, underlying certain order principles andknitting mechanisms.

In contrast, fibrous coatings of the thread-tangles consist of fibers orthreads the position of which can only be described with statisticmethods. The threads also referred to as fibers are arranged in aconfuse, disorderly and random manner to each other. The openings thatarise between the threads are designated as meshes.

The term “mesh” as used herein describes an opening between thesurrounding threads of the thread-tangle coating. The openings are notnecessarily round but can assume any shape because the threads of thethread-tangle coating are oriented and spread in a random manner. So anopening, i.e. a mesh is usually surrounded by several threads. Moreover,the meshes show a certain size distribution. The longitudinal diameterof a mesh is to be understood as the maximum extension of this openingand the transverse diameter is the minimal extension of this opening.The cross-sectional area of a mesh is to be understood as the area ofthis opening, i.e. of this mesh within the surrounding threads.Furthermore, the entireties of the meshes also have an averagelongitudinal diameter as well as an average transverse diameter as wellas an average cross-sectional area. These are the averaged values of theabove defined factors over the entirety of the meshes. The determinationof the number, area and diameter of the single meshes can be done byspectroscopic methods.

In FIG. 4 a wedge-shaped mesh can be seen centrally arranged (dark areain the middle of FIG. 4, the tip of the wedge pointing to the right),which is smaller than the tumor cell lying underneath (the brighter areabeginning directly under the mesh, extending downwards oval andlong-stretched) so that the tumor cell cannot pass the thread-tanglecoating.

The threads of the thread-tangle coating have an average thread diameterin the range of 1 μm to 30 μm, preferably in the range of 1 μm to 20 μm,further preferred in the range of 1 μm to 15 μm, even more preferred inthe range of 1 μm to 10 μm and in particular preferred in the range of 2μm to 7 μm.

The meshes of the thread-tangle coating have an average diameter in therange of 0.01 μm to 1000 μm, preferably in the range of 1 μm to 1000 μm,further preferred in the range of 10 μm to 500 μm, even more preferredin the range of 25 μm to 250 μm and in particular preferred in the rangeof 50 μm to 150 μm.

The meshes of the thread-tangle coating have a certain sizedistribution, wherein size is referred to as the cross-sectional area ofeach single mesh in a vertical top view on the respective mesh and thethereby obtained two-dimensional display.

According to the invention the endoprosthesis can be coated with athread-tangle consisting of a preferably linear polymer or a mixture ofpolymers that may be biodegradable or biostable. The polymer(s) can beselected from the group comprising or consisting of:

Polyurethane, polyethylene terephthalate, polyvinyl chloride, polyvinylester, polyvinyl acetals, polyamides, polyimides, polyacryl-nitriles,polyethers, polyesters such as poly-3-hydroxy butylates, poly-3-hydroxyalkanoates, polyamino acids, polysaccharides, polylactides,polyglycolides, polylactide glycolides, chitosans, carboxyalkylchitosans such as carboxymethyl chitosans, collagen, polyphosphazenes,polystyrenes, polysulfones, silicones as well as derivatives, blockpolymers, co-polymers and mixtures of the afore-mentioned polymers. Inprinciple, all polymers that are biocompatible, not cross-linked andsoluble in a solvent can be used.

The present invention thus relates to methods of coating of biostable orbiodegradable endoprostheses, in particular stents, but also of otherprosthesis and auxiliary materials that remain for longer periods in thebody, wherein these are coated with a polymeric close-meshed ortight-meshed thread-tangle.

Thus the invention also comprises methods for the coating of anendoprosthesis for expanding a vascular lumen, comprising the followingsteps:

-   -   a) providing an endoprosthesis,    -   b) solving a polymer in a volatile solvent,    -   c) applying a polymer-based thread-tangle by means of spraying        or electro spinning on the surface of the endoprosthesis.

Besides spray coating the coating can be also carried out by means ofelectro spinning, wet spinning or melt spinning.

As solvents, preferably those solvents are used that solve the polymerwell and are volatile. As solvents, solvents with a high vapor pressureare preferably used, such as acetone, butanone, pentanone,tetrahydrofuran (THF), benzene, toluene, light petrolether, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), xylene, ethylene glycol,water, methanol, ethanol, propanol, chloroform, methylene chloride,acetic acid ethyl ester, n-hexane, isopropanol, phenol or theirmixtures.

In this inventive method the clogging of the threads of thethread-tangle occurs by the threads themselves, meaning the threadsgenerated only by spraying the solution, with still adhesively moistsurface adhere upon contact against and above each other and herein alsoadditives such as active substances can be incorporated into thethread-tangle, which aren't adhesive or at least don't have to beadhesive. Thus no additional adhesive, cross-linking steps orcross-linking agents are needed that would considerably modify thethread surfaces. The threads of the thread-tangle rather clog due to thepresence of the still sticky threads from the solvent at their contactpoints resulting in a thread-tangle according to the invention. Thus nodissimilar adhesive is needed that would cover the fiber surfaces sothat the fiber-specific effects wouldn't develop. By self-implementingthe cohesion of the thread-tangle by fibers only clogged at the crossingpoints the thread-tangle structure displays also better capillarycharacteristics that favor the absorption of fluid and moisture.Spraying the solution for thread generation can preferably be carriedout by compressed air nozzles. The structure of the thread-tangle andthe thread diameter can be varied by material pressure, variations innozzle outlets, distance between endoprosthesis and nozzle as well as bypolymer concentration. Since the threads are only clogged at theircontact points the whole thread-tangle coating is more flexible andmobile, whereby rupture of the thread-tangle coating during dilatationis avoided.

The thread-tangle coating can be preferably extended up to 10% of itslength without the occurrence of flaws, further preferred up to 100% ofits length, further preferred up to 200% and in particular preferredextended up to 400% of its length, without the occurrence of flaws.

The thread-tangle coating of the inventive endoprosthesis preferably hasa porosity defined as air permeability of 1 to 150 ml [1 to 150ml/(cm²*60 s)], more preferred of 10 to 100 ml [10 to 100 ml/(cm²*60 s)]and particularly preferred as 20 to 50 ml air per square centimeter perminute [ml/(cm²*60 s)] at a pressure difference of 1.2 kPa.

The thread-tangle coating of the inventive endoprosthesis preferably hasa porosity defined as water permeability in the range of 100 to 300ml/cm²*min, particularly of 150 to 250 ml/cm²*min (ml water per squarecentimeter and per minute at Δp=120 mmHg). These water permeabilityvalues were measured according to Weselowski's method of determinationat 120 mm Hg. An inventive endoprosthesis is preferably characterized bythe inventive thread-tangle having meshes and consisting of porousthreads.

These features can be used and adjusted upon requirement so thatessential modalities and multiple possibilities result for the usedpolymeric materials and the resulting coated endoprosthesis. Besides theused polymer or polymeric mixture, key parameters are the threaddiameter, the thread porosity, a varying coating thickness, the meshcross-section, the spraying technique, the solvent etc. Despite of thesame coating procedure these numerous variation options ensure anendoprosthesis that is optimally and individually applicable in allknown vascular diseases.

For example, the thread-tangle coating can be realized in such a waythat a tumor cell has no possibility to intrude between the threads intothe inner lumen (see FIG. 4). Furthermore, this coating mode preventsthat e.g. the luminal surface of the hollow organ e.g. can dry out sincethe adjustable size of the meshes promote a further provision of theinterior surface with moisture, because the thread-tangle coating doesnot separate the interior surface of the hollow organ or body passagelike a continuous impermeable foil from the interior lumen of theendoprosthesis, but only excludes the passaging of bigger particles orof cancer cells, but not the permeation of liquid, water or air. Stentswith a polymeric film-like full-size coating show exactly thesedisadvantages, because exchange of moisture or air is prevented. Whereasthe coated stents according to the invention allow the necessaryexchange processes between vascular wall and lumen and ensure that thestented interior vascular wall area is not isolated of necessaryprocesses and/or substances and thus the healing process is supportedoptimally. According to the field of application the germ-killingprocesses of the own body can prevent or reduce the problematic of germdevelopment.

According to the field of application a further coating on the luminalside of the inventive coated stent with hydrophilic polymers may besupportive.

Likewise a smooth luminal surface can also be desirable such as with atrachea stent, so that the flow of the mucosa is ensured. This can beeasily achieved during application of the inventive coating on theendoprosthesis by mounting the endoprosthesis on a cylindrical metalcore adapted to the diameter of the endoprosthesis, so that no threadscan protrude into the lumen but nevertheless the thread-tangle structureis formed perfectly luminal as well as abluminal. For easier detachmentof the spray coated endoprosthesis from the metal core, eventuallywetting of the interior side with a solvent might be necessary or stentswith lubricated pre-coated stent struts are used for coating.

In further preferred embodiments thread-tangles are used or appliedaccording to the invention which further contain at least oneantiproliferative, antimigratory, anti-angiogenic, anti-inflammatory,anti-restenotic, antiphlogistic, cytostatic, cytotoxic and/oranti-thrombotic agent. This active agent can be contained in acovalently bounded form, or in an adhesively or ionically bounded form.Thereby coated medical products, respectively endoprosthesis areobtained that contain at least one active agent in the thread-tanglecoating, preferably in the form of a drug-releasing coating (drugrelease system). The thread-tangle coating can be manufactured bydissolving the active agent or the active agent mixture in the sprayingsolution and then applying the spraying solution or alternatively byapplying it afterwards to the thread-tangle coating.

It is advantageous herein that the release of the active agent or theactive agent mixture out of the inventive thread-tangle coating does notonly occur were the stent struts are, which is the case with commonstents, but also over the entire diseased area, where the inventivecoated endoprosthesis is implanted. In contrast to commerciallyavailable current drug-eluting stents that are only coated with activeagent in the area of the struts, this leads to a comprehensive provisionof the diseased site with the necessary remedies and not only to apunctual treatment of the affected sites, or even to the treatment ofareas close to a lesion only. Likewise, in comparison to the evencoating of the struts of conventional stents the rather rawthread-tangle texture is helpful for the colonization of the injuredareas with new cells, as their adhesion is facilitated.

The following advantages can be listed for endoprosthesis coated with aninventive coating of a polymeric close-meshed or tight-meshedthread-tangle:

-   -   1. The coating method is universally applicable for the area of        vascular endoprosthesis as well as artificial body passages such        as artificial stomae outlet, bladder catheter, vein catheter, in        short all artificial in- and outlets at or in the body necessary        for a longer period of time and still individually adjustable to        different conditions by the choice of the polymer material,        addition of active agents and the adjustable process parameter        such as mesh size or pore size of the threads.    -   2. The thread-tangle covers the generated non-evenness of the        body passages in the lesioned area and thus provides a        significant and necessary protection e.g. in the case of a        vascular stent from thrombocyte attachments in the lesioned area        and thus constitutes a significant inhibition of the coagulation        cascade initiated by activated thrombocytes, with a resulting        life-threatening hemostasis.    -   3. The lesioned area of the vascular wall is substantially        protected by the thread-tangle coating from activities inside        the cavity so that the healing processes can occur in an optimal        manner.    -   4. The polymeric close-meshed or tight-meshed thread-tangle        coating provides for an additional stability of the body        passages in the lesion area.    -   5. The polymeric close-meshed or tight-meshed thread-tangle        coating serves as a mechanical barrier against        hyperproliferation, tumor growth, new fistula formation and        formation of cysts as well as external bleedings.    -   6. Via the still permeable thread-tangle structure the at least        minimal contact between lumen and vascular wall is maintained,        so that the most necessary requirements such as permeation of        nutrients, moisture, oxygen etc are possible, albeit to a        limited extent.    -   7. The textured surface of the thread-tangle coating provides        for an additional support of the endoprosthesis in the vascular        wall.    -   8. The polymeric close-meshed or tight-meshed thread-tangle        coating provides for a reasonable even distribution of the added        active agent over the entire affected area.    -   9. The significantly larger surface of the thread-tangle coating        of a polymeric close-meshed thread-tangle allows the application        of an increased amount of the active agent.    -   10. Through the significantly larger surface of the coating of a        polymeric close-meshed thread-tangle also those active agents        can be administered that only lead to a successful treatment        over a certain dosis that couldn't be realized with a coating of        the struts only. Thus the inventive coating can broaden the        choice of suitable active agents in a most simple manner.    -   11. Active agents can be mixed directly into the spraying        solution for the thread-tangle forming polymers.    -   12. Active agents can be introduced afterwards by filling the        meshes formed by the threads of the thread-tangle.    -   13. The active agents elute with different speed.    -   14. Active agents can be separated locally from each other, on        one side in the porous or biodegradable polymeric fibers and on        the other side between the thread-tangle forming threads.    -   15. The distribution of the active agents over the entire        endoprosthesis is absolutely uniform despite of local        separations.    -   16. Different active agents can be introduced locally separated,        which both are still uniformly distributed and eluted over the        whole therapeutic area.    -   17. The luminal side of such a coated endoprosthesis can be        smooth, coated or uncoated, with or without active agent,        according to the needs.    -   18. The coating of a polymeric close-meshed or tight-meshed        thread-tangle as well as the texture offer a significantly        larger surface for the most diverse approaches for the treatment        of a lesion in the vascular walls of a body passage than a        common (only on the struts) coated endoprosthesis.    -   19. The partial application of the polymeric close-meshed or        tight-meshed thread-tangle coating allows for a specific        treatment of the diseased site, e.g. a tumor growing into the        lumen from the right side can be stopped with a stent that was        coated only on this side. The opposite side of the        endoprosthesis stays open or will be coated only on the struts.        This variant is also well suitable for treatment of aneurysm.    -   20. The pores formed by the thread-tangle can not only be filled        with active agents but if the need arises can be filled with        other materials and excipients that elute after a short time        together with the active agent or are degraded. Rapidly        degrading polymers as well as active agent carriers and elution        controls can be used just as active agent transfer-accelerators        so called transport mediators or mediators.

Finally, in case of sufficient, preferably time-limited stability thepolymeric close-meshed or tight-meshed thread-tangle coating can also beused even without an endoprosthesis. For this purpose the optionallyactive agent containing thread-tangle is sprayed directly on a mouldingcore. Besides a stent, also ongoing, full-size and tubularendoprosthesis can be coated. Therefore, the thread-tangle optionallycontaining an active agent is directly applied to the endoprosthesis(for example in case of a bladder catheter) or the transport unit.Endoprosthesis remaining temporary in the organism, such as bladdercatheters or vein catheters coated with the thread-tangle and e.g.equipped with antibacterial or anti-inflammatory active agents couldsolve or at least significantly improve the problems of many patientswith permanent catheters.

Such a thread-tangle as coating of a degradable or biodegradableendoprosthesis could slowly degrade under controlled conditions after apreset time without any long-term complications that for example areaccompanied with non-degradable endoprosthesis.

Likewise useful is a biostable or biodegradable thread-tangle on abiodegradable stent. Depending on the field of application abiodegradable thread-tangle can also be advantageous on a removableimplant e.g. the removal of the endoprosthesis after degradation of thebiodegradable thread-tangle. The coating and endoprosthesis can also beconfigured to be biodegradable. Also in this case the use of an activeagent could be reasonable.

Naturally it must be ensured that the coating of a polymericclose-meshed or tight-meshed thread-tangle does not release anyfragments or particles that could lead to life-threatening situations.

Of course, it is also possible to apply the active agent(s) in aseparate coating step either directly on the surface of theendoprosthesis and thereby under the thread-tangle coating or on thethread-tangle coating or under as well as on the thread-tangle coating.

The active agent concentration is preferably in the range of 0.001-500mg per square centimeter coated endoprosthesis surface, i.e. the surfaceis calculated in account of the total surface of the inventivethread-tangle coating.

According to the coating method, the active agent(s) can be situatedunder, in and/or on the thread-tangle coating. As antiproliferative,anti-inflammatory, antimigratory, antiphlogistic, anti-angiogenic,cytostatic, cytotoxic, anti-restenotic, anti-neoplastic, anti-bacterialand/or anti-mycotic agent can be used preferably:

Abciximab, acemetacin, acetylvismione B, aclarubicin, ademetionine,adriamycin, aescin, afromoson, akagerine, aldesleukin, amidorone,aminoglutethemide, amsacrine, anakinra, anastrozole, anemonin,aminopterine, antimycotics, antithrombotics, apocymarin, argatroban,aristolactam-All, aristolochic acid, ascomycin, asparaginase, aspirin,atorvastatin, auranofin, azathioprine, azithromycin, baccatine,bafilomycin, basiliximab, bendamustine, benzocaine, berberine, betulin,betulinic acid, bilobol, bisparthenolidine, bleomycin, bombrestatin,Boswellic acids and derivatives thereof, bruceanoles A, B and C,bryophyllin A, busulfan, antithrombin, bivalirudin, cadherins,camptothecin, capecitabine, o-carbamoyl-phenoxy-acetic acid,carboplatin, carmustine, celecoxib, cepharanthin, cerivastatin, CETPinhibitors, chlorambucil, chloroquine phosphate, cicutoxin,ciprofloxacin, cisplatin, cladribine, clarithromycin, colchicine,concanamycin, coumadin, C-type Natriuretic Peptide (CNP),cudraisoflavone A, curcumin, cyclophosphamide, cyclosporine A,cytarabine, dacarbazine, daclizumab, dactinomycin, dapson, daunorubicin,diclofenac, 1,11-dimethoxycanthin-6-one, docetaxel, doxorubicin,daunomycin, epirubicin, epothilones A and B, erythromycin, estramustine,etoposide, everolimus, filgrastim, fluoroblastin, fluvastatin,fludarabine, fludarabine-5′-dihydrogenphosphate, fluorouracil,folimycin, fosfestrol, gemcitabine, ghalakinoside, ginkgol, ginkgolicacid, glycoside 1a, 4-hydroxyoxycyclophosphamide, idarubicin,ifosfamide, josamycin, lapachol, lomustine, lovastatin, melphalan,midecamycin, mitoxantrone, nimustine, pitavastatin, pravastatin,procarbazine, mitomycin, methotrexate, mercaptopurine, thioguanine,oxaliplatin, irinotecan, topotecan, hydroxycarbamide, miltefosine,pentostatin, pegaspargase, exemestane, letrozole, formestane,mitoxantrone, mycophenolate mofetil, β-lapachone, podophyllotoxin,podophyllic acid 2-ethylhydrazide, molgramostim (rhuGM-CSF),peginterferon α-2b, lenograstim (r-HuG-CSF), macrogol, selectin(cytokine antagonist), cytokinin inhibitors, COX-2 inhibitor,angiopeptin, monoclonal antibodies which inhibit muscle cellproliferation, bFGF antagonists, probucol, prostaglandins,1-hydroxy-11-methoxycanthin-6-one, scopoletin, NO donors,pentaerythritol tetranitrate and sydnonimines, S-nitrosoderivatives,tamoxifen, staurosporine, β-estradiol, α-estradiol estriol, estrone,ethinylestradiol, medroxyprogesterone, estradiol cypionates, estradiolbenzoates, tranilast, kamebakaurin and other terpenoids used in cancertherapy, verapamil, tyrosine kinase inhibitors (tyrphostins), paclitaxeland its derivatives, 6-α-hydroxy-paclitaxel, taxotere, mofebutazone,lonazolac, lidocaine, ketoprofen, mefenamic acid, piroxicam, meloxicam,penicillamine, hydroxychloroquine, sodium aurothiomalate, oxaceprol,6-sitosterin, myrtecaine, polidocanol, nonivamide, levomenthol,ellipticine, D-24851 (Calbiochem), colcemid, cytochalasin A-E,indanocine, nocadazole, bacitracin, vitronectin receptor antagonists,azelastine, guanidyl cyclase stimulator tissue inhibitor of metalproteinase-1 and -2, free nucleic acids, nucleic acids incorporated intovirus transmitters, DNA and RNA fragments, plasminogen activatorinhibitor-1, plasminogen activator inhibitor-2, antisenseoligonucleotides, VEGF inhibitors, IGF-1, active agents from the groupof antibiotics, cefadroxil, cefazolin, cefaclor, cefoxitin, tobramycin,gentamycin, penicillins, dicloxacillin, oxacillin, sulfonamides,metronidazole, enoxaparin, heparin, hirudin, PPACK, protamine,prourokinase, streptokinase, warfarin, urokinase, vasodilators,dipyridamol, trapidil, nitroprussides, PDGF antagonists,triazolopyrimidine, seramin, ACE inhibitors, captopril, cilazapril,lisinopril, enalapril, losartan, thioprotease inhibitors, prostacyclin,vapiprost, interferon α, β and γ, histamine antagonists, serotoninblockers, apoptosis inhibitors, apoptosis regulators, halofuginone,nifedipine, paracetamol, dexpanthenol, clopidogrel, acetylsalicylic acidderivatives, streptomycin, neomycin, framycetin, paromomycin,ribostamycin, kanamycin, amikacin, arbekacin, bekanamycin, dibekacin,spectinomycin, hygromycin b, paromomycinsulfate, netilmicin, sisomicin,isepamicin, verdamicin, astromicin, apramycin, geneticin, amoxicillin,ampicillin, bacampicillin, pivmecillinam, flucloxacillin, mezlocillin,piperacillin, azlocillin, temocillin, ticarcillin, amoxicillin,clavulanic acid, ampicillin, sulbactam, piperacillin, tazobactam,sulbactam, cefamandol, cefotiam, cefuroxim, cefmenoxim, cefodizim,cefoperazon, cefotaxim, ceftazidim, cefsulodin, ceftriaxon, cefepim,cefpirom, cefoxitin, cefotetan, cefalexin, cefuroxim axetil, cefixim,cefpodoxim, ceftibuten, imipenem, meropenem, ertapenem, doripenem,aztreonam, spiramycin, azithromycin, telithromycin, quinopristin,dalfopristin, clindamycin, tetracycline, doxycyclin, minocyclin,trimethoprim, sulfamethoxazol, sulfametrol, nitrofurantoin,lomefloxacin, norfloxacin, ciprofloxacin, ofloxacin, fleroxacin,levofloxacin, sparfloxacin, moxifloxacin, vancomycin, teicoplanin,linezolid, daptomycin, rifampicin, fusidic acid, fosfomycin, trometamol,chloramphenicol, metronidazol, colistin, mupirocin, bacitracin,neomycin, fluconazol, itraconazol, voriconazol, posaconazol,amphotericin b, 5-flucytosin, caspofungin, anidulafungin, tocopherol,tranilast, molsidomine, tea polyphenols, epicatechin gallate,epigallocatechin gallate, leflunomide, etanercept, sulfasalazine,etoposide, dicloxacillin, tetracycline, triamcinolone, mutamycin,procainimide, retinoic acid, quinidine, disopyramide, flecamide,propafenone, sotolol, natural and synthetically obtained steroids,inotodiol, maquiroside A, ghalakinoside, mansonine, strebloside,hydrocortisone, betamethasone, dexamethasone, non-steroidal substances(NSAIDS), fenoprofen, ibuprofen, indomethacin, naproxen, phenylbutazone,antiviral agents, acyclovir, ganciclovir, zidovudin, clotrimazole,flucytosine, griseofulvin, ketoconazole, miconazole, nystatin,terbinafine, antiprotozoal agents, chloroquine, mefloquine, quinine,natural terpenoids, hippocaesculin, Barringtogenol-C21-angelat,14-dehydroagrostistachin, agroskerin, agrostistachin,17-hydroxyagrostistachin, ovatodiolids, 4,7-oxycycloanisomelic acid,baccharinoids B1, B2, B3 and B7, tubeimoside, bruceantinoside C,yadanziosides N and P, isodeoxyelephantopin, tomenphantopin A and B,Coronarin A, B, C und D, ursolic acid, hyptatic acid A,iso-iridogermanal, maytenfoliol, effusantin A, excisanin A and B,longikaurin B, sculponeatin C, kamebaunin, leukamenin A and B,13,18-Dehydro-6-alpha-senecioyloxychaparrin, taxamairin A and B,regenilol, triptolide, cymarin, hydroxyanopterin, protoanemonin,cheliburin chloride, sinococuline A and B, dihydronitidine, nitidinechloride, 12-beta-hydroxypregnadien-3,20-dion, helenalin, indicine,indicine-N-oxide, lasiocarpine, inotodiol, podophyllotoxin, justicidin Aand B, larreatin, malloterin, mallotochromanol,isobutyrylmallotochromanol, maquiroside A, marchantin A, maytansine,lycoridicin, margetine, pancratistatin, liriodenine, bisparthenolidine,oxoushinsunine, periplocoside A, ursolic acid, deoxypsorospermin,psycorubin, ricin A, sanguinarine, manwu wheat acid, methylsorbifolin,sphatheliachromen, stizophyllin, mansonine, strebloside,dihydrousambaraensine, hydroxyusambarine, strychnopentamine,strychnophylline, usambarine, usambarensine, liriodenine,oxoushinsunine, daphnoretin, lariciresinol, methoxylariciresinol,syringaresinol, sirolimus (rapamycin) and its derivatives such asbiolimus A9, everolimus, myolimus, novolimus, pimecrolimus,ridaforolimus, deoxorapamycin, tacrolimus FK 506, temsirolimus andzotarolimus, somatostatin, tacrolimus, roxithromycin, troleandomycin,simvastatin, rosuvastatin, vinblastine, vincristine, vindesine,teniposide, vinorelbine, trofosfamide, treosulfan, temozolomide,thiotepa, tretinoin, spiramycin, umbelliferone, desacetylvismione A,vismione A and B, zeorin and sulfur containing amino acids such ascystine as well as salts, hydrates, solvates, enantiomers, racemates,enantiomer mixtures, diastereomers mixtures; metabolites, prodrugs andmixtures of the aforementioned active agents.

The thread-tangle coating or the meshes of the thread-tangle coating maybe sealed with a resorbable or under the working conditions resistableimpregnation. These can also contain an active agent, which is releasedin a controlled manner. Furthermore, the meshes formed by thethread-tangle can be filled with a resorbable polymer or oligomer or aviscous substance, containing an active substance or being itself theactive substance.

Furthermore, in a step anterior to the coating step with thethread-tangle a hemocompatible layer can be immobilized on the surfacepreferably bound in a covalent manner on the uncoated endoprosthesissurface, or by cross-linkage e.g. with glutaraldehyde. Such a layer thatdoesn't activate blood coagulation is reasonable in those cases whenuncoated stent material may come into contact with blood. Thus it ispreferred to provide a partially coated stent with this interiorhemocompatible layer first. Alternatively, also an exterior, optionallyhemocompatible layer can be applied on the thread-tangle coating.“Interior” layer or coating indicates the layer or coating which isapplied directly on the stent surface. “Exterior” layer or coatingindicates the layer or coating which is the top one or the most distantone from the stent surface.

The preferably hemocompatible layer is produced from the followingpreferred materials: Heparin of native origin as well asregioselectively produced derivatives of different degrees ofsulfatation and acetylation in the molecular weight range of thepentasaccharide responsible for the antithrombotic effect to thestandard molecular weight of commercially available heparin of ca. 13kD, heparan sulfates and its derivatives, oligo- and polysaccharides ofthe erythrocyte glycol calyx, oligosaccharides, polysaccharides,completely desulfated and N-reacetylated heparin, desulfated andN-reacetylated heparin, N-carboxymethylated and/or partiallyN-acetylated chitosan, polyacrylic acid, polyether ether ketones,polyvinyl pyrrolidone and/or polyethylene glycol as well as mixtures ofthese compounds.

The inventive methods are suitable for the coating of for exampleendoprosthesis, and particularly stents such as coronary stents,vascular stents, trachea stents, bronchial stents, urethra stents,esophageal stents, bile duct stents, kidney stents, small intestinestents, colon stents, cerebral stent, pharynx stent, periphery stent andother stents. Moreover, spirals, catheters, cannulas, tubes, guidewires, as well as generally tubular or hose-like implants or parts ofthe aforementioned medical products can be coated according to theinvention.

The endoprosthesis and particularly the stent may consist of currentmaterials such as medical stainless steel, titanium, chrome, vanadium,tungsten, molybdenum, gold, iron, cobalt-chrome, Nitinol, magnesium,iron, alloys of the aforementioned metals as well as of bioresorbablemetals and metal alloys such as magnesium, zinc, calcium, iron and so onas well as of polymeric material and preferably resorbable polymericmaterial such as chitosan, heparans, polyhydroxy butyrates (PHB),polyglycerides, polylactides and co-polymers of the afore-mentionedcompounds. A catheter can be manufactured of any of the currentmaterials in particular polymers such as polyamide, polyether,polyurethane, polyacrylates, polyethers and other polymers.

The coated medical products are used especially for keeping open alltubular structures, such as the urinary tract, oesophagus, trachea, bileduct, kidney ducts, blood vessels in the entire body including thebrain, nose, duodenum, pylorus, small and large intestine, but also forkeeping open artificial outlets such as used for the intestines or thetrachea and also for keeping open long-term necessary artificial in- andoutlets.

Thus the coated medical products are suitable for preventing, reducingor treating stenoses, restenoses, in-stent restenoses, arteriosclerosis,atherosclerosis, tumors, fistula formation, formation of cysts,aneurysm, bleeding in surrounding tissue and all other forms of vascularocclusions, vascular constrictions, vascular dilations and injuries ofpassages or outlets or artificial in- and outlets.

A further embodiment of the present invention relates to anendoprosthesis with a porous wall of synthetic polymer, whereinmicroparticles are embedded in the wall of the prosthesis on the surfaceof which blood coagulation inhibitors are immobilized. The bloodcoagulation inhibitors are preferably immobilized on the surface of themicroparticles via so-called linkers (spacer molecules). Generally, thelinkers are not covalently, but preferably adsorptively bound to themicroparticle. The blood coagulation inhibitors are preferablycovalently bound to the linkers. The covalent bondage is normally basedon a chemical condensation reaction between functional groups of thelinkers and suitable reactive groups of the inhibitors, for examplehydroxy and/or amino groups. Through bondage with the linkers the bloodcoagulation inhibitors are at a certain distance to the microparticles.Thereby activity impairments of the inhibitors can be widely avoided.The immobilization of the linker-inhibitor conjugate on themicroparticle surfaces is preferably based on adsorptive, particularlyelectrostatic interactions between the linkers and the microparticlesurfaces.

In other preferred embodiments the linkers are polymeric molecules,conveniently with a linear structure. Preferably, these linkers areoligo- or polyalkylene glycols, in particular polyethylene glycol (PEG).The blood coagulation inhibitors are preferably serine proteaseinhibitors, in particular thrombin inhibitors. Thrombin is the keyenzyme of plasmatic blood coagulation, cleaving fibrinogen to monomericfibrin. The latter is polymerizing in the following and cross-linksblood components adhered at the vascular wall inside to a thrombus.

DESCRIPTION OF FIGURES

FIG. 1 shows a PLGA thread-tangle around a partially pre-expanded stent,having been crimped and expanded after coating with the thread-tangle.It can be easily recognized that the PLGA sleeve has stayed intact.

FIG. 2 shows a thread-tangle coated stent with micropores (d=200 μm; ddenotes the average pore diameter).

FIG. 3 shows, in comparison to FIGS. 1 and 2, a not pre-expandedendoprosthesis with a burst open PLGA thread-tangle coating aftercrimping and expansion attempts. The stent was overextended such thatthe thread-tangle coating ruptured, allowing a good look at thethread-like coating structure. Under physiological conditions such astent overextension does not occur so there is no danger that thethread-tangle coating ruptures.

FIG. 4 shows a tumor cell that due to its size is not able to penetrateto the other side of the thread-tangle coating.

FIG. 5 shows a REM-picture of a PU-fiber-web or rather fiber-tanglemanufactured by spraying method on stainless steel gauze (1000×magnification). The white circles correspond to approximately 5 μm andshall give an impression of the fiber diameter. The flat areas areformed by agglutination of overlying fibers during the spraying process.The estimated pore size of the smallest pores is between 2 and 5 μm forboth materials (Estimation in 10 k-pictures according to the smallcircles corresponding to approximately 5 μm). The structure of the innerand outer surface of the material does not differ substantially.

FIG. 6 shows a REM-picture of a PU-fiber-web or rather fiber-tanglemanufactured by spraying method on stainless steel gauze (800×magnification). The flat areas are formed by agglutination of overlyingfibers during the spraying process. The estimated pore size of thesmallest pores is between 2 and 5 μm for both materials (Estimation in10 k-pictures according to the small circles corresponding toapproximately 5 μm). The structure of the inner and outer surface of thematerial does not differ substantially.

FIG. 7 shows the endoprosthesis in different phases of coating. A)Endoprosthesis before coating, mounted horizontal on a rod of thecoating device; B) coated endoprosthesis, mounted horizontal on a rod ofthe coating device; C) coated endoprosthesis.

EXAMPLES Example 1 Pre-Coating of the Struts of the Endoprosthesis witha Polymer

The struts of an endoprosthesis were spray-coated with a 0.5% PLGAsolution. To this aim, the stent is hung horizontally on a thin metalrod which is stuck on the rotational axis of the rotation and forwardfeed device, rotating with a defined rotatory speed. At a definedamplitude of the forward feed and rotatory speed and a defined distancebetween stent and nozzle the stent is sprayed with the spray solution.After drying at room temperature and storing in the exhaust hood overnight it is weighed again. The pre-coating of the stent struts orendoprosthesis struts provides for a better adhesion of thethread-tangle on the struts.

Example 2 Full-Size Pre-Coating of the Struts of the Endoprosthesis withan Anti-Proliferative Active Agent Containing Polymer

Spray solution: 145.2 mg PLGA or polysulfone and 48.4 mg rapamycin or a33% spray solution of a corresponding active agent combination ofrapamycin (amount 20%-90%) with one or more further active agents suchas paclitaxel, cyclosporine A, thalidomide, fusadil etc. are filled upwith chloroform to 22 g.

This spray solution is applied on the stent as already described inexample 1.

The stent can be a bare stent, a hemocompatible coated stent and/or astent coated with an active agent layer by spray or dipping method.

The spray solution for coating merely the struts has in general anotheractive agent than the following thread-tangle spray coating.

Example 3 Pre-Coating of the Endoprosthesis on the Example of aTransurethral or Suprapubic Catheter with an Anti-Bacterial Active AgentContaining Polymer

Solution: 144.5 mg PVP and a 32% spray solution of a correspondinganti-bacterial and anti-fungicide active agent combination (e.g.erythromycin and terbinafin 3:1 w:w) is filled up with chloroform to 22g.

This spray solution is applied to the surface as described in example 1full-size, uniformly and without any gaps according to the spray method(dipping method also possible).

Example 4 Full-Size or Strut-Interstices-Overlapping Full-Size Coatingof the Endoprosthesis with a PLGA Thread-Tangle

After drying the partially pre-expanded endoprosthesis is sprayed with aPLGA solution containing 3% chloroform on the same spray coating deviceas in Example 1 in order to apply a dense moisture permeablethread-tangle.

Example 5 Production of a Full-Size or Strut-Interstices-OverlappingFull-Size Thread-Tangle Coated Endoprosthesis with a Smooth InteriorWall and PU-Thread-Tangle Coating on the Exterior Surface

An endoprosthesis is firmly mounted on a polished stainless steel rodand dipped into a viscous polyurethane (PU) solution in THF (ca. 16%)(e.g. chronoflex C 65D from Avansource Biomaterials Inc.).

On the slightly dried surface an uniform thread-tangle layer is appliedin the following with a 6% PU solution in THF by means of the sprayingdevice (e.g. Chronoflex C 80A). After drying the such thread-tanglecoated stent is removed carefully from the metal rod.

Example 6A Thread-Tangle Coating on an Endoprosthesis Crimped on aBalloon Catheter

The pre-treated stent is crimped on a balloon catheter and subsequentlyfull-size coated with a 5% PLGA spraying solution (Resomer RG504H fromEvonik with an inherent viscosity of 0.54 dl/g) in chloroform accordingto example 2.

Example 7A Strut-Interstices-Overlapping Full-Size Coating of Stentswith a PDLG-Thread-Tangle

Each 10 stents were pre-sprayed on the struts only with a 0.5%PDLG-solution (Purasorb PDLG 5010 from PURAC with an inherent viscosityof 1.03 dl/g) this pre-coating ensuring a better adhesion of thethread-tangle on the struts. After drying the stents were sprayed with a3% PDLG-solution to apply a dense thread-tangle. The coating was sprayedover the right and left edges of the stent such that the turning pointslay outside of the stent.

The PLGA-thread-tangle coating on the non-expanded stent as well as thecoating of the 100% pre-expanded stent ruptured after crimping on theballoon catheter and expansion to 4 mm diameter. The PDGL-thread-tanglecoating of the 50% pre-expanded stent remained intact during crimpingand expansion. The functionality of the coating of the 50% pre-expandedstent was still unchanged after storage for 5-days without an inertatmosphere.

Example 6B Hemocompatible Coating of an Endoprosthesis with DesulfatedReacetylated Heparin

Non-expanded stents made of medical stainless steel LVM 316 aredegreased with acetone and ethanol in the ultrasound bath for 15 minutesand dried in the drying cabinet at 100° C. Subsequently, they are dippedinto a 2% 3-aminopropyl triethoxysilane solution in an ethanol/watermixture (50/50 (v/v)) for 5 minutes and then dried at 100° C. for 5minutes. Afterwards the stents are washed overnight in demineralizedwater.

3 mg desulfated and reacetylated heparin are solved at 4° C. in 30 ml0.1 M MES buffer (2-(N-morpholino)ethanesulfonic acid) pH 4.75 and 30 mgN-cyclohexyl-N′-(2-morpholinoethyl)carbodiimide-methyl-p-toluenesulfonate are added. The stents are stirred in this solution at 4° C.for 15 hours. Afterwards it is rinsed with water, 4 M NaCl solution andwater for 2 hours each.

Example 7B Hemocompatible Coating of an Endoprosthesis Coated with aThread-Tangle of Polyurethane

The same method for hemocompatible coating of surfaces as shown inexample 6B and 3 can be applied on the thread-tangle of e.g. PU andthereby produce an endoprosthesis with a hemocompatible surface with athread-tangle.

Example 8 Manufacturing of an Endoprosthesis with a Smooth Interior Walland Sprayed Exterior Wall on the Example of Polyurethane

A polished stainless steel rod is used as carrier material for thedipping/spraying process for manufacturing the vascular prosthesis ofpolyurethane.

The metal rod is initially dipped in a viscous PU-solution (e.g.carbothane PC-3575A) in THF in order to obtain a smooth interior wall.Subsequently, a 6% polyurethane-THF-solution is sprayed on thepre-coated metal rod. After drying the endoprosthesis is incubated for30 min in a bath with SDS-solution at 60° C. and then is detached fromthe metal rod. The so obtained endoprosthesis has a wall strength of 1mm.

The wall strength is adjustable through the spraying process. Thedesired range of the wall strength is preferably between 1 and 1.5 mm.The diameter as well as the length of the endoprosthesis is variable anddepends from the diameter and length of the stainless steel rod.

Example 9 Coating of Endoprosthesis with a Thread-Tangle ofPolycarbonaturethane with Admixture of a Tenside (Tween 20)

For the spray-thread-tangle 1.5% to 6% polycarbonat urethane solutionsin THF with an amount of tenside of 5%, 10% and 20% based on theproportions of solids in the solutions is manufactured.

During the coating with polycarbonat urethane-tenside-THF-solution thecylinder is moved back and forth in a longitudinal direction with adefined speed and at the same time is rotated around its longitudinalaxis.

The higher the polymer concentration in spraying solution the thickerare the resulting threads. At low concentrations only very thin threadsdevelop, wherein the structure is agglutinated by spray solutionsdroplets.

With increasing layer thickness the thread-tangles display a betterwetting and spreading behavior for water. (However, the differentconcentrations of the tenside scarcely have any influence on thespreading behavior of water or water-like liquids or the wettingbehavior of the thread-tangle surface.)

The thread-tangle is applied as uniformly as possible. Depending on thesprayed endoprosthesis the layer thickness is varied. In case of theherein described surfaces it is for example not thicker than 20 μm.

Example 10 Coating of an Expandable Esophagus Stent with a MolecularPermeable Thread-Tangle of Biostable Polymeric Fibers

Spraying solution with a high amount of a hydrophilic polymer:

Polyethersulfone/PVP—solution: 24.0 mg PS and 1.4 mg PVP are weighed andfilled up with chloroform to 3 g→0.80% PS, 0.047% PVP

Optionally, according to example 1 only a strut coating basic layer ofpolyethersulfone may be applied with or without active agent, with orwithout hydrophilic polymeric additive to the polyethersulfone.

Spraying Solution with Active Agent Examples

-   a) PS/simvastatin/PVP-solution:    -   23.2 mg PS, 8.8 mg simvastatin and 3.2 mg PVP are weighed and        filled up to 4 g with chloroform→0.58% PS, 0.22% simvastatin,        0.08% PCP    -   b. 13.2 mg PS and 4.4 mg paclitaxel are weighed and filled up to        2 g with chloroform→0.66% PS, 0.22% paclitaxel    -   c. 11.6 mg PS, 3 mg PVP and 4.4 mg paclitaxel are weighed and        filled up to 2 g with chloroform→0.58% PS, 0.15 PVP, 0.22%        paclitaxel

Active agents or active agent combinations can be solved in chloroformup to ca. 40 percent by weight with polyethersulfone and the admixtureof an intrafilamentous permeability enhancing hydrogel such as PVP, PVAand other hydrophilic polymers, resulting in a solution with at least0.04% hydrogel that can be applied to an endoprosthesis.

The pores formed by the thread-tangle are loaded afterwards withrapamycin by dipping the stent coated with the thread-tangle in anactive agent solution (2% solution in a volatile solvent).

Example 11 Interfilamentary Active Agent Containing Thread-TangleCoating of an Endoprosthesis

The endoprosthesis according to example 8, but without the addition of atenside, is coated with the thread-tangle. Subsequently, the filamentinterstices are filled with an active agent containing solution bydipping method and exploiting the capillary properties of the coating.

b) Likewise it is possible to apply a pure active agent layer on thethread-tangle coating by spraying the surface with a solution with adefined amount of active agent and subsequent drying.

c) The thread-tangle coating can also be loaded in a most easily mannerwith another or the same active agent by dipping it in an active agentcontaining solution. By means of capillary forces the pores of thethread-tangle are filled with active agent.

d) In the same way the different active agents can be appliedseparately, for example e) filling of the pores of the thread-tanglewith agents, will accelerate the uptake of active agent in the vascularwall.

e) Filling of the pores with short-term biodegradable polymers such asPLGA 50/50, that can release the active agent controlled andtime-displaced.

f) Combination of the aforementioned possible variations.

1. Endoprosthesis with a surface having at least partially a coating ofa polymeric close-meshed or tight-meshed thread-tangle. 2.Endoprosthesis according to claim 1, wherein the thread-tangle consistsof at least one biostable or biodegradable polymer selected from thegroup comprising or consisting of: Polyurethane, polyethyleneterephthalate, polyvinyl chloride, polyvinyl ester, polyvinyl acetalespolyamides, polyimides, polyacrylnitriles, polyethers, polyesters,polyamino acids, polysaccharides, polylactides, polyglycolides,polylactide-co-glycolides, chitosans, carboxyalkyl chitosans, collagen,polyethylene glycol, polyvinyl pyrrolidone, polyphosphazenes,polystyrenes, polysulfones as well as derivatives, block polymers,co-polymers and mixtures of the aforementioned polymers. 3.Endoprosthesis according to claim 1, wherein the thread-tangle coatinghas meshes.
 4. Endoprosthesis according to claim 3, wherein the mesheshave an average transverse diameter in the range of 0.01 μm to 1.000 μmand/or an average longitudinal diameter in the range of 0.01 μm to 1.000μm.
 5. Endoprosthesis according to claim 1, wherein the threads of thethread-tangle coating are porous.
 6. Endoprosthesis according to claim1, wherein the thread-tangle coating has a porosity defined as airpermeability of 1 to 150 ml air per square centimeter per minute at apressure difference of 1.2 kPa.
 7. Endoprosthesis according to claim 1,wherein the thread-tangle coating has a porosity defined as waterpermeability of 100 to 300 ml/(cm²*min) and in particular of 150 to 250ml/(cm²*min).
 8. Endoprosthesis according to claim 1, further comprisingat least one antiproliferative, anti-inflammatory, antimigratory,antiphlogistic, anti-angiogenic, cytostatic, cytotoxic, anti-restenotic,anti-neoplasic, anti-bacterial and/or anti-mycotic agent. 9.Endoprosthesis according to claim 8, wherein the at least oneantiproliferative, anti-inflammatory, antimigratory, antiphlogistic,anti-angiogenic, cytostatic, cytotoxic, anti-restenotic, anti-neoplasic,anti-bacterial and/or anti-mycotic agent is selected from the groupcomprising or consisting of: Abciximab, acemetacin, acetylvismione B,aclarubicin, ademetionine, adriamycin, aescin, afromoson, akagerine,aldesleukin, amidorone, aminoglutethemide, amsacrine, anakinra,anastrozole, anemonin, aminopterine, antimycotics, antithrombotics,apocymarin, argatroban, aristolactam-All, aristolochic acid, ascomycin,asparaginase, aspirin, atorvastatin, auranofin, azathioprine,azithromycin, baccatine, bafilomycin, basiliximab, bendamustine,benzocaine, berberine, betulin, betulinic acid, bilobol,bisparthenolidine, bleomycin, bombrestatin, Boswellic acids andderivatives thereof, bruceanoles A, B and C, bryophyllin A, busulfan,antithrombin, bivalirudin, cadherins, camptothecin, capecitabine,o-carbamoyl-phenoxy-acetic acid, carboplatin, carmustine, celecoxib,cepharanthin, cerivastatin, CETP inhibitors, chlorambucil, chloroquinephosphate, cicutoxin, ciprofloxacin, cisplatin, cladribine,clarithromycin, colchicine, concanamycin, coumadin, C-type NatriureticPeptide (CNP), cudraisoflavone A, curcumin, cyclophosphamide,cyclosporine A, cytarabine, dacarbazine, daclizumab, dactinomycin,dapson, daunorubicin, diclofenac, 1,11-dimethoxycanthin-6-one,docetaxel, doxorubicin, daunomycin, epirubicin, epothilones A and B,erythromycin, estramustine, etoposide, everolimus, filgrastim,fluoroblastin, fluvastatin, fludarabine,fludarabine-5′-dihydrogenphosphate, fluorouracil, folimycin, fosfestrol,gemcitabine, ghalakinoside, ginkgol, ginkgolic acid, glycoside 1a,4-hydroxyoxycyclophosphamide, idarubicin, ifosfamide, josamycin,lapachol, lomustine, lovastatin, melphalan, midecamycin, mitoxantrone,nimustine, pitavastatin, pravastatin, procarbazine, mitomycin,methotrexate, mercaptopurine, thioguanine, oxaliplatin, irinotecan,topotecan, hydroxycarbamide, miltefosine, pentostatin, pegaspargase,exemestane, letrozole, formestane, mitoxantrone, mycophenolate mofetil,β-lapachone, podophyllotoxin, podophyllic acid 2-ethylhydrazide,molgramostim (rhuGM-CSF), peginterferon α-2b, lenograstim (r-HuG-CSF),macrogol, selectin (cytokine antagonist), cytokinin inhibitors, COX-2inhibitor, angiopeptin, monoclonal antibodies which inhibit muscle cellproliferation, bFGF antagonists, probucol, prostaglandins,1-hydroxy-11-methoxycanthin-6-one, scopoletin, NO donors,pentaerythritol tetranitrate and sydnonimines, S-nitrosoderivatives,tamoxifen, staurosporine, □-estradiol, □-estradiol, estriol, estrone,ethinylestradiol, medroxyprogesterone, estradiol cypionates, estradiolbenzoates, tranilast, kamebakaurin, terpenoides, verapamil, tyrosinekinase inhibitors, tyrphostins, paclitaxel and its derivatives,6-α-hydroxy-paclitaxel, taxotere, mofebutazone, lonazolac, lidocaine,ketoprofen, mefenamic acid, piroxicam, meloxicam, penicillamine,hydroxychloroquine, sodium aurothiomalate, oxaceprol, β-sitosterin,myrtecaine, polidocanol, nonivamide, levomenthol, ellipticine, colcemid,cytochalasin A-E, indanocine, nocadazole, bacitracin, vitronectinreceptor antagonists, azelastine, guanidyl cyclase stimulator, tissueinhibitor of metal proteinase-1 and -2, free nucleic acids, nucleicacids incorporated into virus transmitters, DNA and RNA fragments,plasminogen activator inhibitor-1, plasminogen activator inhibitor-2,antisense oligonucleotides, VEGF inhibitors, IGF-1, antibiotics,cefadroxil, cefazolin, cefaclor, cefoxitin, tobramycin, gentamycin,penicillins, dicloxacillin, oxacillin, sulfonamides, metronidazole,enoxaparin, heparin, hirudin, PPACK, protamine, prourokinase,streptokinase, warfarin, urokinase, vasodilators, dipyridamol, trapidil,nitroprussides, PDGF antagonists, triazolopyrimidine, seramin, ACEinhibitors, captopril, cilazapril, lisinopril, enalapril, losartan,thioprotease inhibitors, prostacyclin, vapiprost, interferon α, β and γ,histamine antagonists, serotonin blockers, apoptosis inhibitors,apoptosis regulators, halofuginone, nifedipine, tocopherol, tranilast,molsidomine, tea polyphenols, epicatechin gallate, epigallocatechingallate, leflunomide, etanercept, sulfasalazine, etoposide,dicloxacillin, tetracycline, triamcinolone, mutamycin, procainimide,retinoic acid, quinidine, disopyramide, flecamide, propafenone, sotolol,natural and synthetically obtained steroids, inotodiol, maquiroside A,ghalakinoside, mansonine, strebloside, hydrocortisone, betamethasone,dexamethasone, non-steroidal substances (NSAIDS), fenoprofen, ibuprofen,indomethacin, naproxen, phenylbutazone, antiviral agents, acyclovir,ganciclovir, zidovudin, clotrimazole, flucytosine, griseofulvin,ketoconazole, miconazole, nystatin, terbinafine, antiprotozoal agents,chloroquine, mefloquine, quinine, natural terpenoids, hippocaesculin,Barringtogenol-C21-angelat, 14-dehydroagrostistachin, agroskerin,agrostistachin, 17-hydroxyagrostistachin, ovatodiolids,4,7-oxycycloanisomelic acid, baccharinoids B1, B2, B3 and B7,tubeimoside, bruceantinoside C, yadanziosides N and P,isodeoxyelephantopin, tomenphantopin A and B, Coronarin A, B, C und D,ursolic acid, hyptatic acid A, iso-iridogermanal, maytenfoliol,effusantin A, excisanin A and B, longikaurin B, sculponeatin C,kamebaunin, leukamenin A and B,13,18-Dehydro-6-alpha-senecioyloxychaparrin, taxamairin A and B,regenilol, triptolide, cymarin, hydroxyanopterin, protoanemonin,cheliburin chloride, sinococuline A and B, dihydronitidine, nitidinechloride, 12-beta-hydroxypregnadien-3,20-dion, helenalin, indicine,indicine-N-oxide, lasiocarpine, inotodiol, podophyllotoxin, justicidin Aand B, larreatin, malloterin, mallotochromanol,isobutyrylmallotochromanol, maquiroside A, marchantin A, maytansine,lycoridicin, margetine, pancratistatin, liriodenine, bisparthenolidine,oxoushinsunine, periplocoside A, ursolic acid, deoxypsorospermin,psycorubin, ricin A, sanguinarine, manwu wheat acid, methylsorbifolin,sphatheliachromen, stizophyllin, mansonine, strebloside,dihydrousambaraensine, hydroxyusambarine, strychnopentamine,strychnophylline, usambarine, usambarensine, liriodenine,oxoushinsunine, daphnoretin, lariciresinol, methoxylariciresinol,syringaresinol, sirolimus and its derivatives such as biolimus A9,everolimus, myolimus, novolimus, pimecrolimus, ridaforolimus, tacrolimusFK 506, temsirolimus and zotarolimus, somatostatin, roxithromycin,troleandomycin, simvastatin, rosuvastatin, vinblastine, vincristine,vindesine, teniposide, vinorelbine, trofosfamide, treosulfan,temozolomide, thiotepa, tretinoin, spiramycin, umbelliferone,desacetylvismione A, zeorin, vismione A and vismione B. 10.Endoprosthesis according to claim 1, wherein the endoprosthesis isprovided with an exterior hemocompatible layer and/or an interiorhemocompatible layer.
 11. Endoprosthesis according to claim 1, whereinthe endoprosthesis is a stent.
 12. Endoprosthesis according to claim 1for preventing, reducing or treating lesions of the wall of bodypassages, stenosis, restenosis, in-stent restenosis, late stentthrombosis, arteriosclerosis, vascular occlusions, vascularconstrictions, constricted heart valves, aneurysms, artificial outletsand inlets to the human body and laying a lumen in the human body. 13.Method for coating of an endoprosthesis comprising the following steps:a) providing an endoprosthesis, b) solving a polymer in a volatilesolvent, c) applying of a thread-tangle of the polymer by means ofspraying or electrospinning on the surface of the endoprosthesis. 14.Endoprosthesis according to claim 2, wherein the thread-tangle coatinghas meshes.
 15. Endoprosthesis according to claim 2, wherein the threadsof the thread-tangle coating are porous.
 16. Endoprosthesis according toclaim 2, wherein the thread-tangle coating has a porosity defined as airpermeability of 1 to 150 ml air per square centimeter per minute at apressure difference of 1.2 kPa.
 17. Endoprosthesis according to claim 2,wherein the thread-tangle coating has a porosity defined as waterpermeability of 100 to 300 ml/(cm²*min) and in particular of 150 to 250ml/(cm²*min).
 18. Endoprosthesis according to claim 2, wherein theendoprosthesis is provided with an exterior hemocompatible layer and/oran interior hemocompatible layer.
 19. Endoprosthesis according to claim2, wherein the endoprosthesis is a stent.
 20. Endoprosthesis accordingany to claim 2 for preventing, reducing or treating lesions of the wallof body passages, stenosis, restenosis, in-stent restenosis, late stentthrombosis, arteriosclerosis, vascular occlusions, vascularconstrictions, constricted heart valves, aneurysms, artificial outletsand inlets to the human body and laying a lumen in the human body.